Cerebral Protection in Transcatheter Aortic Valve Replacement

Cerebral Protection in Transcatheter Aortic Valve Replacement - The SENTINEL Study

The Sentinel System will be a safe and effective method for capturing and removing embolic material (thrombus/debris) during transcatheter aortic valve replacement in order to reduce the ischemic burden in the cerebral anterior circulation.

The Sentinel™ Cerebral Protection System is indicated for use as an embolic capture and retrieval system intended to reduce the ischemic burden in the cerebral anterior circulation while performing transcatheter aortic valve replacement.

The objective of this study is to assess the safety and efficacy of the Claret Medical Sentinel Cerebral Protection System used for embolic protection during Transcatheter Aortic Valve Replacement (TAVR) compared to TAVR standard of care (without embolic protection).

The study population is comprised of subjects with severe symptomatic calcified native aortic valve stenosis who meet the commercially approved indications for TAVR with the Edwards SAPIEN THV or SAPIEN XT and comply with the inclusion/exclusion criteria.

Inclusion Criteria:

1. Approved indications for commercially available Edwards SAPIEN Transcatheter Heart Valve, model 9000TFX or SAPIEN XT, model 9300TFX meeting one of the three sub-criteria below:

   SAPIEN

   1. transfemoral delivery in subjects with severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency and with ejection fraction >20% who have been examined by a heart team including an experienced cardiac surgeon and a cardiologist and found to either be:

      1. inoperable and in whom existing co-morbidities would not preclude the expected benefit from correction of the aortic stenosis; or
      2. be operative candidates for aortic valve replacement but who have a Society of Thoracic Surgeons predicted operative risk score >8% or are judged by the heart team to be at a 15% risk of mortality for surgical aortic valve replacement.

      or

   2. transapical delivery in subjects with severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency and with ejection fraction > 20% who have been examined by a heart team including an experienced cardiac surgeon and a cardiologist and found to be operative candidates for aortic valve replacement but who have a Society of Thoracic Surgeons operative risk score 8% or are judged by the heart team to be at a 15% risk of mortality for surgical aortic valve replacement.

      SAPIEN XT (Transfemoral or Transapical only)

   3. in patients with symptomatic heart disease due to severe native calcific aortic stenosis (aortic valve area ≤ 1.0 cm2 or aortic valve area index ≤ 0.6 cm2/m2, a mean aortic valve gradient of ≥ 40 mmHg, or a peak aortic-jet velocity of ≥ 4.0 m/s), and with native anatomy appropriate for the 23, 26, or 29 mm valve system, who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score ≥8% or at a ≥15% risk of mortality at 30 days).

2. Compatible left common carotid artery (6.5 - 10 mm) and brachiocephalic artery (9 - 15 mm) diameters without significant stenosis (> 70%) as determined by Multi-Slice Computed Tomography (MSCT) scan or equivalent imaging modality

3. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visit

4. The subject or the subject's legal representative has been informed of the nature of the trial, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site

Exclusion Criteria:

General

1. Vasculature in the right extremity precluding 6Fr sheath radial or brachial access

2. Inadequate circulation to the right extremity as evidenced by signs of artery occlusion (modified Allen's test) or absence of radial/brachial pulse

3. Hemodialysis shunt, graft, or arterio-venous fistula involving the upper extremity vasculature

4. Evidence of an acute myocardial infarction ≤ 1 month before the intended treatment

5. Aortic valve is a congenital unicuspid or bicuspid valve; or is non-calcified

6. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation >3+)

7. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (unless part of planned strategy for treatment of concomitant coronary artery disease)

8. Pre-existing prosthetic heart valve in any position, prosthetic ring, or severe (greater than 3+) mitral insufficiency

9. Blood dyscrasias as defined: Leukopenia, acute anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy

10. Hemodynamic instability requiring inotropic support or mechanical heart assistance.

11. Need for emergency surgery for any reason

12. Hypertrophic cardiomyopathy with or without obstruction

13. Severe ventricular dysfunction with LVEF ≤20%

14. Echocardiographic evidence of intracardiac or aortic mass, thrombus, or vegetation

15. Symptomatic or asymptomatic severe occlusive carotid disease requiring concomitant CEA/stenting

16. Subject has undergone carotid stenting or carotid endarterectomy within the previous 6 weeks

17. Active peptic ulcer or upper GI bleeding within the prior 3 months

18. A known hypersensitivity or contraindication to aspirin, heparin, ticlopidine, or clopidogrel, or sensitivity to contrast media, which cannot be adequately pre-medicated

19. Recent (within 6 months) CVA or a TIA

20. Renal insufficiency (creatinine > 3.0 mg/dL or GFR < 30) and/or renal replacement therapy at the time of screening

21. Life expectancy < 12 months due to non-cardiac co-morbid conditions

22. Subjects in whom anti-platelet and/or anticoagulant therapy is contraindicated, or who will refuse transfusion

23. Subjects who have active bacterial endocarditis or other active infections

24. Currently participating in an investigational drug or another device study

25. Subjects who have a planned treatment with any other investigational device or procedure during the study follow-up period (90 days)

26. Subject with planned concomitant surgical or transcatheter ablation for Atrial Fibrillation during the study follow-up period (90 days)

27. Any subject with a balloon valvuloplasty (BAV) within 30 days of the procedure

    Neurologic

28. Subject had active major psychiatric disease

29. Subject has severe visual, auditory, or learning impairment and who are unable to comprehend English and therefore unable to be consented for the study

30. Subjects with neurodegenerative or other progressive neurological disease or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities

    Angiographic

31. Excessive tortuosity in the right radial/brachial/subclavian artery preventing Sentinel System access and insertion

32. Subject whose brachiocephalic or left carotid artery reveals significant stenosis, calcification, ectasia, dissection, or aneurysm at the ostium or within 3 cm of the ostium

    Magnetic Resonance Imaging

33. Subject Body Mass Index (BMI) precluding imaging in scanner

34. Contraindications to MRI (subjects with any implantable temporary or permanent pacemaker or defibrillator, metal implants in field of view, metallic fragments, clips, or devices in the brain or eye before TAVR procedure)

35. Planned implantation of a pacemaker or defibrillator implantation after TAVR

36. Claustrophobia

37. Known allergy to gadolinium or contrast agent